Identification of Major Trypanosoma Cruzi Antigenic Determinants in Chronic Chagas' Heart Disease

Levìn, Mariano J.; Mesri, Enrique A.; Bénarous, Richard; Levitus, Gabriela; Schijman, Alejandro G.; Levy-Yeyati, Patricia; Chiale, Pablo A.; Ruiz, Andrés M.; Kahn, Axel; Rosenbaum, Mauricio B.; Torres, Héctor N.; Segura, Elsa L.

doi:10.4269/ajtmh.1989.41.530

Cited by 118 publications

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“…These sequences are highly conserved throughout evolution and share more than 90% homology with the C-terminal regions of the human ribosomal P proteins, which are in turn the target of anti-P autoantibodies in SLE (16). Analysis of the reactivities of anti-P autoantibodies and antibodies directed against the parasite P proteins in cChHD showed that they share the same specificity (7,8,27). This observation led several authors to conclude that mechanisms active in generating the anti-P autoimmune response in SLE are also operative in the generation of the anti-P response in Chagas disease, and could contribute to cChHD pathogenesis (27,28).…”

Section: Discussionmentioning

confidence: 99%

“…Molecular expression cloning techniques showed that patients with overt Chagas heart disease present a strong humoral response against the C-terminal end of the low molecular weight ribosomal P proteins of T. cruzi (7,8). These sequences are highly conserved throughout evolution and share more than 90% homology with the C-terminal regions of the human ribosomal P proteins, which are in turn the target of anti-P autoantibodies in SLE (16).…”

Section: Discussionmentioning

confidence: 99%

“…In our search for serological markers of chronically active myocardial damage in human T. cruzi infection, we found that sera from patients with overt Chagas heart disease recognized predominantly, among other antigenic determinants, the Cterminal regions of the T. cruzi ribosomal P proteins (7)(8)(9). Two B cell epitopes were found to be implicated.…”

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confidence: 99%

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Antibodies to ribosomal P proteins ofTrypanosoma cruziin Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus

Kaplan

Ferrari

Bergami

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the Cterminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the ␤ 1 -adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the ␤ 1 adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-␤ 1 receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergicstimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Antibodies to ribosomal P proteins ofTrypanosoma cruziin Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus

Kaplan

Ferrari

Bergami

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…Several recombinant proteins allow specific and sensitive detection of antibodies directed against T. cruzi. Recombinant proteins have been proposed as stage or pathological specific markers while others should be relevant for cure criteria (Affranchino et al 1989, Levin et al 1989, Mesri et al 1990, Aznar et al 1995, Gomes 1997, Guevara et al 1997.…”

Section: Integrate Study Of a Bolivian Population Infected Bymentioning

confidence: 99%

Integrate Study of a Bolivian Population Infected by Trypanosoma cruzi, the Agent of Chagas Disease

Brenière

Noireau

Yacsik

et al. 2002

Mem. Inst. Oswaldo Cruz

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“…Moreover, specific epitopes associated with the host immune response and potentially able to produce myocardial damage have been recently identified 120,[154][155][156][157][158][159][160][161][162] . There is also evidence that persistent T. cruzi antigen presentation to macrophages could lead to cytokyne production, thus modulating the immune response and possibly causing the relative immunosuppressive state responsible for perpetuation of infection 121,163,164 .…”

Section: Pathophysiology and Pathogenetic Mechanismsmentioning

confidence: 99%

Chagas' heart disease

Marin-Neto¹,

Simões²,

Sarabanda³

1999

Arq. Bras. Cardiol.

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Identification of Major Trypanosoma Cruzi Antigenic Determinants in Chronic Chagas' Heart Disease

Cited by 118 publications

References 0 publications

Antibodies to ribosomal P proteins ofTrypanosoma cruziin Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus

Antibodies to ribosomal P proteins ofTrypanosoma cruziin Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus

Integrate Study of a Bolivian Population Infected by Trypanosoma cruzi, the Agent of Chagas Disease

Chagas' heart disease

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